In MRI, the contrast in the images generated may be enhanced by introducing into the zone being imaged an agent, generally referred to as a contrast agent, which affects the nuclear spin reequilibration characteristics of the nuclei (generally water protons in body tissues or fluids) which are responsible for the magnetic resonance signals from which the MR images are generated.
Thus, for example, in 1978 Lauterbur proposed the use of paramagnetic species, such as Mn(II), as MRI contrast agents (see Lauterbur et al., pages 752-759 in "Electrons to Tissues - Frontiers of Biological Energetics", Volume 1, edited by Dutton et al., Academic Press, N.Y., 1978) and more recently Schering AG, in U.S. Pat. No. 4647447, proposed the use of the dimeglumine salt of the gadolinium (III) chelate of diethylenetriaminepentaacetic acid (Gd DTPA).
Gadolinium (III) compounds are particularly attractive as MRI contrast agents due to the large magnetic dipole of Gd.sup.3+.
However, the usefulness of even high stability constant chelates such as Gd DTPA could be limited since the dosage required for imaging certain organs may possibly be too toxic for safe and effective use and, as Schering AG have themselves disclosed, there is a problem of gadolinium retention following iv administration of Gd DTPA (see AU-81889/87).
Gd DTPA-bis(hydroxylated alkylamides) have proven to be substantially less toxic than Gd DTPA and thus to be utilizable in higher dosages and for imaging of a wider variety of organs than Gd DTPA. Gd DTPA-bis(hydoxylated alkylamides) are disclosed in U.S. Pat. No. 4826673 (Dean) and EP-A-130934 (Schering AG).
The present invention provides compositions containing DTPA-bis(hydroxylated alkylamide) (DTPA-BHA) chelates of both gadolinium and calcium, compositions which exhibit lower toxicities than Gd DTPA or Gd and DTPA-BHA, and which can therefore be safely administered in even higher doses than Gd DTPA or Gd DTPA-BHA.